Dynamic Nonlinear Spatial Integrations on Encoding Contrasting Stimuli of Tectal Neurons.

Animals detect targets using a variety of visual cues, with the visual salience of these cues determining which environmental features receive priority attention and further processing. Surround modulation plays a crucial role in generating visual saliency, which has been extensively studied in avian tectal neurons. Recent work has reported that the suppression of tectal neurons induced by motion contrasting stimulus is stronger than that by luminance contrasting stimulus. However, the underlying mechanism remains poorly understood. In this study, we built a computational model (called Generalized Linear-Dynamic Modulation) which incorporates independent nonlinear tuning mechanisms for excitatory and inhibitory inputs. This model aims to describe how tectal neurons encode contrasting stimuli. The results showed that: (1) The dynamic nonlinear integration structure substantially improved the accuracy (significant difference (p < 0.001, paired t-test) in the goodness of fit between the two models) of the predicted responses to contrasting stimuli, verifying the nonlinear processing performed by tectal neurons. (2) The modulation difference between luminance and motion contrasting stimuli emerged from the predicted response by the full model but not by that with only excitatory synaptic input (spatial luminance: 89 ± 2.8% (GL_DM) vs. 87 ± 2.1% (GL_DMexc); motion contrasting stimuli: 87 ± 1.7% (GL_DM) vs. 83 ± 2.2% (GL_DMexc)). These results validate the proposed model and further suggest the role of dynamic nonlinear spatial integrations in contextual visual information processing, especially in spatial integration, which is important for object detection performed by birds.

Visual shape discrimination in goldfish, modelled with the neural circuitry of optic tectum and torus longitudinalis.

There is no satisfactory neurally-based theory as to how vertebrates that lack a neocortex discriminate even simple geometric shapes. In fishes, an intact optic tectum is necessary for such discriminations, but physiological studies of it have found nothing like the hierarchically arranged feature detecting neurons of mammalian visual cortex. Here, a neural model attempts a solution by basing shape discrimination upon the responses of only those elementary detectors (e.g. of size) that are within a focus of attention, formed by a winner-take-all arrangement of retinotopically mapped units representing tectal pyramidal cells. While this relatively primitive mechanism could recognize an object irrespective of position in space, it fails to distinguish patterns that differ only in their features' spatial relationships. The model's solution - imitating goldfish that naturally attend to the top of shapes - is to shift attention to the edges of a shape by spatially offsetting inputs to the pyramidal neurons, effected by the torus longitudinalis and its prolific synapses on pyramidal dendrites. The model's shape discrimination was compared to an extensive behavioral study using shapes with points and projections. In one test series fish were sensitive to the relative number of points on the tops of shapes. In another, fish were trained to discriminate points on the sides. By using different offset connections and only one elementary feature detector for small dark spots, the model successfully emulated the two sets of goldfish data, as judged by significant correlations between model response and fish discrimination.

Turbidity drives plasticity in the eyes and brains of an African cichlid.

Natural variation in environmental turbidity correlates with variation in the visual sensory system of many fishes, suggesting that turbidity may act as a strong selective agent on visual systems. Since many aquatic systems experience increased turbidity due to anthropogenic perturbations, it is important to understand the degree to which fish can respond to rapid shifts in their visual environment, and whether such responses can occur within the lifetime of an individual. We examined whether developmental exposure to turbidity (clear, <5 NTU; turbid, ∼9 NTU) influenced the size of morphological structures associated with vision in the African blue-lip cichlid Pseudocrenilabrus multicolor. Parental fish were collected from two sites (clear swamp, turbid river) in western Uganda. F1 broods from each population were split and reared under clear and turbid rearing treatments until maturity. We measured morphological traits associated with the visual sensory system (eye diameter, pupil diameter, axial length, brain mass, optic tectum volume) over the course of development. Age was significant in explaining variation in visual traits even when standardized for body size, suggesting an ontogenetic shift in the relative size of eyes and brains. When age groups were analyzed separately, young fish reared in turbid water grew larger eyes than fish reared in clear conditions. Population was important in the older age category, with swamp-origin fish having relatively larger eyes and optic lobes relative to river-origin fish. Plastic responses during development may be important for coping with a more variable visual environment associated with anthropogenically induced turbidity.

Mapping the avian visual tectofugal pathway using 3D reconstruction.

Image processing in amniotes is usually accomplished by the thalamofugal and/or tectofugal visual systems. In laterally eyed birds, the tectofugal system dominates with functions such as color and motion processing, spatial orientation, stimulus identification, and localization. This makes it a critical system for complex avian behavior. Here, the brains of chicks, Gallus gallus, were used to produce serial brain sections in either coronal, sagittal, or horizontal planes and stained with either Nissl and Gallyas silver myelin or Luxol fast blue stain and cresyl echt violet (CEV). The emerging techniques of diffusible iodine-based contrast-enhanced computed tomography (diceCT) coupled with serial histochemistry in three planes were used to generate a comprehensive three-dimensional (3D) model of the avian tectofugal visual system. This enabled the 3D reconstruction of tectofugal circuits, including the three primary neuronal projections. Specifically, major components of the system included four regions of the retina, layers of the optic tectum, subdivisions of the nucleus rotundus in the thalamus, the entopallium in the forebrain, and supplementary components connecting into or out of this major avian visual sensory system. The resulting 3D model enabled a better understanding of the structural components and connectivity of this complex system by providing a complete spatial organization that occupied several distinct brain regions. We demonstrate how pairing diceCT with traditional histochemistry is an effective means to improve the understanding of, and thereby should generate insights into, anatomical and functional properties of complicated neural pathways, and we recommend this approach to clarify enigmatic properties of these pathways.

Topography of visual and somatosensory inputs to the pontine nuclei in zebra finches (Taeniopygia guttata).

Birds have a comprehensive network of sensorimotor projections extending from the forebrain and midbrain to the cerebellum via the pontine nuclei, but the organization of these circuits in the pons is not thoroughly described. Inputs to the pontine nuclei include two retinorecipient areas, nucleus lentiformis mesencephali (LM) and nucleus of the basal optic root (nBOR), which are important structures for analyzing optic flow. Other crucial regions for visuomotor control include the retinorecipient ventral lateral geniculate nucleus (GLv), and optic tectum (TeO). These visual areas, together with the somatosensory area of the anterior (rostral) Wulst, which is homologous to the primary somatosensory cortex in mammals, project to the medial and lateral pontine nuclei (PM, PL). In this study, we used injections of fluorescent tracers to study the organization of these visual and somatosensory inputs to the pontine nuclei in zebra finches. We found a topographic organization of inputs to PM and PL. The PM has a lateral subdivision that predominantly receives projections from the ipsilateral anterior Wulst. The medial PM receives bands of inputs from the ipsilateral GLv and the nucleus laminaris precommisulis, located medial to LM. We also found that the lateral PL receives a strong ipsilateral projection from TeO, while the medial PL and region between the PM and PL receive less prominent projections from nBOR, bilaterally. We discuss these results in the context of the organization of pontine inputs to the cerebellum and possible functional implications of diverse somato-motor and visuomotor inputs and parcellation in the pontine nuclei.

Unravelling the functional development of vertebrate pathways controlling gaze.

Animals constantly redirect their gaze away or towards relevant targets and, besides these goal-oriented responses, stabilizing movements clamp the visual scene avoiding image blurring. The vestibulo-ocular (VOR) and the optokinetic reflexes are the main contributors to gaze stabilization, whereas the optic tectum integrates multisensory information and generates orienting/evasive gaze movements in all vertebrates. Lampreys show a unique stepwise development of the visual system whose understanding provides important insights into the evolution and development of vertebrate vision. Although the developmental emergence of the visual components, and the retinofugal pathways have been described, the functional development of the visual system and the development of the downstream pathways controlling gaze are still unknown. Here, we show that VOR followed by light-evoked eye movements are the first to appear already in larvae, despite their burrowed lifestyle. However, the circuits controlling goal-oriented responses emerge later, in larvae in non-parasitic lampreys but during late metamorphosis in parasitic lampreys. The appearance of stabilizing responses earlier than goal-oriented in the lamprey development shows a stepwise transition from simpler to more complex visual systems, offering a unique opportunity to isolate the functioning of their underlying circuits.

Radial astrocyte synchronization modulates the visual system during behavioral-state transitions.

Glial cells support the function of neurons. Recent evidence shows that astrocytes are also involved in brain computations. To explore whether and how their excitable nature affects brain computations and motor behaviors, we used two-photon Ca2+ imaging of zebrafish larvae expressing GCaMP in both neurons and radial astrocytes (RAs). We found that in the optic tectum, RAs synchronize their Ca2+ transients immediately after the end of an escape behavior. Using optogenetics, ablations, and a genetically encoded norepinephrine sensor, we observed that RA synchronous Ca2+ events are mediated by the locus coeruleus (LC)-norepinephrine circuit. RA synchronization did not induce direct excitation or inhibition of tectal neurons. Nevertheless, it modulated the direction selectivity and the long-distance functional correlations among neurons. This mechanism supports freezing behavior following a switch to an alerted state. These results show that LC-mediated neuro-glial interactions modulate the visual system during transitions between behavioral states.

Increased neuron density in the midbrain of a foveate bird, pigeon, results from profound change in tissue morphogenesis.

The increase of brain neuron number in relation with brain size is currently considered to be the major evolutionary path to high cognitive power in amniotes. However, how changes in neuron density did contribute to the evolution of the information-processing capacity of the brain remains unanswered. High neuron densities are seen as the main reason why the fovea located at the visual center of the retina is responsible for sharp vision in birds and primates. The emergence of foveal vision is considered as a breakthrough innovation in visual system evolution. We found that neuron densities in the largest visual center of the midbrain - i.e., the optic tectum - are two to four times higher in modern birds with one or two foveae compared to birds deprived of this specialty. Interspecies comparisons enabled us to identify elements of a hitherto unknown developmental process set up by foveate birds for increasing neuron density in the upper layers of their optic tectum. The late progenitor cells that generate these neurons proliferate in a ventricular zone that can expand only radially. In this particular context, the number of cells in ontogenetic columns increases, thereby setting the conditions for higher cell densities in the upper layers once neurons did migrate.

Comparative neurotoxicity of dietary methylmercury and waterborne inorganic mercury in fish: Evidence of optic tectum vulnerability through morphometric and histopathological assessments.

This work investigated the effects of inorganic mercury (iHg) and methylmercury (MeHg) on the fish optic tectum morphology, viz. in relation to: (i) vulnerability of specific optic tectum layers; (ii) preferential targeting of Hg forms to neurons or glial cells; (iii) comparative toxicity of iHg and MeHg in this brain area that is in the maintenance of several fish behaviors. Two experiments exposing juvenile white seabream (Diplodus sargus) to waterborne iHg [HgCl2 (2 µg L-1)] and dietary MeHg (8.7 µg g-1) were performed, comprising both exposure (7 and 14 days; E7 and E14, respectively) and post-exposure (28 days; PE28) periods. Morphometric assessments were performed using stereological methods where the layers of the optic tectum were outlined, while its area and the number of neurons and glial cells were estimated. A histopathological assessment was also performed per section and per layer of optic tectum. iHg exposure did not trigger the loss of neurons during the exposure periods, while a decrease of glial cells was detected in a single layer of the optic tectum at E14. Differently, upon MeHg exposure, a decrease on the number of neurons and glial cells was found in several layers of optic tectum. In the post-exposure, both Hg forms triggered the loss of neurons, while only MeHg exposure led to a decrease on the number of glia cells. The histopathological assessment pointed out a higher toxicity of MeHg in the optic tectum layers, particularly in the post-exposure period, while no significant alterations were found in fish exposed to iHg. Hg forms targeted preferentially neurons. iHg and MeHg are relevant neurotoxicants to fish, with MeHg exposure leading to a higher toxicity than iHg in the optic tectum. After 28 days of post-exposure, iHg and MeHg neurotoxicity remained prominent, suggesting long-term effects of these toxicants.

Cell-autonomous and differential endocannabinoid signaling impacts the development of presynaptic retinal ganglion cell axon connectivity in vivo.

Cannabis exposure during gestation evokes significant molecular modifications to neurodevelopmental programs leading to neurophysiological and behavioral abnormalities in humans. The main neuronal receptor for Δ9-tetrahydrocannabinol (THC) is the type-1 cannabinoid receptor CB1R, one of the most abundant G-protein-coupled receptors in the nervous system. While THC is the major psychoactive phytocannabinoid, endocannabinoids (eCBs) are the endogenous ligands of CB1R and are known to act as retrograde messengers to modulate synaptic plasticity at different time scales in the adult brain. Accumulating evidence indicates that eCB signaling through activation of CB1R plays a central role in neural development. During development, most CB1R localized to axons of projection neurons, and in mice eCB signaling impacts axon fasciculation. Understanding of eCB-mediated structural plasticity during development, however, requires the identification of the precise spatial and temporal dynamics of CB1R-mediated modifications at the level of individual neurons in the intact brain. Here, the cell-autonomous role of CB1R and the effects of CB1R-mediated eCB signaling were investigated using targeted single-cell knockdown and pharmacologic treatments in Xenopus. We imaged axonal arbors of retinal ganglion cells (RGCs) in real time following downregulation of CB1R via morpholino (MO) knockdown. We also analyzed RGC axons with altered eCB signaling following treatment with URB597, a selective inhibitor of the enzyme that degrades Anandamide (AEA), or JZL184, an inhibitor of the enzyme that blocks 2-Arachidonoylglycerol (2-AG) hydrolysis, at two distinct stages of retinotectal development. Our results demonstrate that CB1R knockdown impacts RGC axon branching at their target and that differential 2-AG and AEA-mediated eCB signaling contributes to presynaptic structural connectivity at the time that axons terminate and when retinotectal synaptic connections are made. Altering CB1R levels through CB1R MO knockdown similarly impacted dendritic morphology of tectal neurons, thus supporting both pre- and postsynaptic cell-autonomous roles for CB1R-mediated eCB signaling.

Ascending Visual Pathways to the Telencephalon in Teleosts with Special Focus on Forebrain Visual Centers, Associated Neural Circuitries, and Evolution.

Visual pathways to the telencephalon in teleost fishes have been studied in detail only in a few species, and their evolutionary history remained unclear. On the basis of our recent studies we propose that there were two visual pathways in the common ancestor of teleosts, while one of them became lost in acanthopterygian fishes that emerged relatively recently. Our in-depth analyses on the connections of visual centers also revealed that there are connections shared with those of mammals, and retinotopic organization of the ascending connections is maintained at least to the level of the diencephalon in the yellowfin goby. The major visual telencephalic center, or the lateral part of the dorsal telencephalon (Dl), shows considerable species differences in the number of regions and cytoarchitecture. In particular, four highly specialized compartments are noted in the Dl of gobies, and we analyzed about 100 species of teleosts to investigate the evolution of the compartments in the Dl, which indicated that four compartments emerged only in Gobiiformes, while there are fewer specialized compartments in some other percomorph lineages. We also discuss the connections of forebrain visual centers with the cerebellum and other lower brain centers and infer possible functions of the circuitries.

Responses of the in vitro turtle brain to visual and auditory stimuli during severe hypoxia.

North American pond turtles (Emydidae) are renowned for their ability to survive extreme hypoxia and anoxia, which enables several species to overwinter in ice-locked, anoxic freshwater ponds and bogs for months. Centrally important for surviving these conditions is a profound metabolic suppression, which enables ATP demands to be met entirely with glycolysis. To better understand whether anoxia limits special sensory functions, we recorded evoked potentials in a reduced brain preparation, in vitro, that was perfused with severely hypoxic artificial cerebral spinal fluid (aCSF). For recordings of visual responses, an LED was flashed onto retinal eyecups while evoked potentials were recorded from the retina or the optic tectum. For recordings of auditory responses, a piezomotor-controlled glass actuator displaced the tympanic membrane while evoked potentials were recorded from the cochlear nuclei. We found that visual responses decreased when perfused with hypoxic perfusate (aCSF PO2<4.0 kPa). In contrast, the evoked response within the cochlear nuclei was unattenuated. These data provide further support that pond turtles have a limited ability to sense visual information in their environment even while moderately hypoxic, but that auditory input may become a principal avenue of sensory perception during extreme diving in this species such as occurs during anoxic submergence.

Recurrent network interactions explain tectal response variability and experience-dependent behavior.

Response variability is an essential and universal feature of sensory processing and behavior. It arises from fluctuations in the internal state of the brain, which modulate how sensory information is represented and transformed to guide behavioral actions. In part, brain state is shaped by recent network activity, fed back through recurrent connections to modulate neuronal excitability. However, the degree to which these interactions influence response variability and the spatial and temporal scales across which they operate, are poorly understood. Here, we combined population recordings and modeling to gain insights into how neuronal activity modulates network state and thereby impacts visually evoked activity and behavior. First, we performed cellular-resolution calcium imaging of the optic tectum to monitor ongoing activity, the pattern of which is both a cause and consequence of changes in network state. We developed a minimal network model incorporating fast, short range, recurrent excitation and long-lasting, activity-dependent suppression that reproduced a hallmark property of tectal activity - intermittent bursting. We next used the model to estimate the excitability state of tectal neurons based on recent activity history and found that this explained a portion of the trial-to-trial variability in visually evoked responses, as well as spatially selective response adaptation. Moreover, these dynamics also predicted behavioral trends such as selective habituation of visually evoked prey-catching. Overall, we demonstrate that a simple recurrent interaction motif can be used to estimate the effect of activity upon the incidental state of a neural network and account for experience-dependent effects on sensory encoding and visually guided behavior.

From perception to behavior: The neural circuits underlying prey hunting in larval zebrafish.

A key challenge for neural systems is to extract relevant information from the environment and make appropriate behavioral responses. The larval zebrafish offers an exciting opportunity for studying these sensing processes and sensory-motor transformations. Prey hunting is an instinctual behavior of zebrafish that requires the brain to extract and combine different attributes of the sensory input and form appropriate motor outputs. Due to its small size and transparency the larval zebrafish brain allows optical recording of whole-brain activity to reveal the neural mechanisms involved in prey hunting and capture. In this review we discuss how the larval zebrafish brain processes visual information to identify and locate prey, the neural circuits governing the generation of motor commands in response to prey, how hunting behavior can be modulated by internal states and experience, and some outstanding questions for the field.

Tangentially migrating cells differentiate into stratum griseum central neurons to form tectofugal visual pathway in the developing chick optic tectum.

BACKGROUND: The optic tectum is the main visual processor of nonmammalian vertebrates and relays visual information from the eye to the telencephalon via the tectofugal pathway. In the development of the avian optic tectum, while the multipolar neurons are arranged by tangential migration, the behavior of individual cells in tangential migration, neural differentiation, and cell fate remain unclear. Here, we pursued the transition of tangentially migrating cells and their involvement in visual circuit formation during chick development. RESULTS: After tangential movement along the axons, the migrating cells relocated to the upper layers and turned back upon differentiation toward the multipolar neurons. The multipolar neurons are destined to differentiate into the stratum griseum central (SGC) neurons with the large dendritic field, which form the tectorotundal projection. Trans-synaptic virus labeling demonstrated that the tangentially migrating cells eventually participate in the tectofugal visual pathway. CONCLUSIONS: These results indicate that tangential migration is a crucial process in the formation of the tectofugal visual pathway during the development of the optic tectum.

Sub-chronic administration of fluoxetine does not alter prey-capture or predator avoidance behaviors in adult South African clawed frogs (Xenopus laevis).

Animals will halt foraging efforts and engage defensive behaviors in response to predator cues. Some researchers have proposed that the switch from appetitive to avoidance behavior resembles anxiety, but most work on this has been performed in a limited number of animal models, primarily zebrafish and rodents. We used adult South African clawed frogs (Xenopus laevis) to determine if the canonical anxiolytic fluoxetine alters predator-induced changes in appetitive and avoidance behavior in a laboratory-based trade-off task that mimics foraging/predator avoidance tradeoffs in the wild. We hypothesized that sub-chronic fluoxetine treatment (20 d) would not affect baseline behavior but would reverse predator-induced changes in food intake, appetitive and avoidance behavior, and the abundance of anxiety related gene transcripts in the optic tectum, a brain area central to ecological decision making in frogs. We found that fluoxetine significantly reduced baseline locomotion compared to vehicle-treated animals. Fluoxetine had no effect on appetitive and avoidance behaviors that were sensitive to predator cues in this assay and did not alter any of the anxiety-related transcripts in the tectum. We conclude that while peripheral sub-chronic administration of fluoxetine significantly reduces locomotion, it does not modify predator-induced changes in approach and avoidance behaviors in this assay. Our findings are not consistent with visual predator cues causing state anxiety in adult frogs.

fmr1 Mutation Alters the Early Development of Sensory Coding and Hunting and Social Behaviors in Larval Zebrafish.

Autism spectrum disorders (ASDs) are developmental in origin; however, little is known about how they affect the early development of behavior and sensory coding. The most common inherited form of autism is Fragile X syndrome (FXS), caused by a mutation in FMR1 Mutation of fmr1 in zebrafish causes anxiety-like behavior, hyperactivity, and hypersensitivity in auditory and visual processing. Here, we show that zebrafish fmr1-/- mutant larvae of either sex also display changes in hunting behavior, tectal coding, and social interaction. During hunting, they were less successful at catching prey and displayed altered behavioral sequences. In the tectum, representations of prey-like stimuli were more diffuse and had higher dimensionality. In a social behavioral assay, they spent more time observing a conspecific but responded more slowly to social cues. However, when given a choice of rearing environment fmr1-/- larvae preferred one with reduced visual stimulation, and rearing them in this environment reduced genotype-specific effects on tectal excitability. Together, these results shed new light on how fmr1-/- changes the early development of neural systems and behavior in a vertebrate.SIGNIFICANCE STATEMENT Autism spectrum disorders (ASDs) are caused by changes in early neural development. Animal models of ASDs offer the opportunity to study these developmental processes in greater detail than in humans. Here, we found that a zebrafish mutant for a gene which in humans causes one type of ASD showed early alterations in hunting behavior, social behavior, and how visual stimuli are represented in the brain. However, we also found that mutant fish preferred reduced visual stimulation, and rearing them in this environment reduced alterations in neural activity patterns. These results suggest interesting new directions for using zebrafish as a model to study the development of brain and behavior in ASDs, and how the impact of ASDs could potentially be reduced.

A blinking focal pattern of re-entrant activity in the avian tectum.

Re-entrant connections are inherent to nervous system organization; however, a comprehensive understanding of their operation is still lacking. In birds, topographically organized re-entrant signals, carried by axons from the nucleus-isthmi-parvocellularis (Ipc), are distinctly recorded as bursting discharges across the optic tectum (TeO). Here, we used up to 48 microelectrodes regularly spaced on the superficial tectal layers of anesthetized pigeons to characterize the spatial-temporal pattern of this axonal re-entrant activity in response to different visual stimulation. We found that a brief luminous spot triggered repetitive waves of bursting discharges that, appearing from initial sources, propagated horizontally to areas representing up to 28° of visual space, widely exceeding the area activated by the retinal fibers. In response to visual motion, successive burst waves started along and around the stimulated tectal path, tracking the stimulus in discontinuous steps. When two stimuli were presented, the burst-wave sources alternated between the activated tectal loci, as if only one source could be active at any given time. Because these re-entrant signals boost the retinal input to higher visual areas, their peculiar dynamics mimic a blinking "spotlight," similar to the internal searching mechanism classically used to explain spatial attention. Tectal re-entry from Ipc is thus highly structured and intrinsically discontinuous, and higher tectofugal areas, which lack retinotopic organization, will thus receive incoming visual activity in a sequential and piecemeal fashion. We anticipate that analogous re-entrant patterns, perhaps hidden in less bi-dimensionally organized topographies, may organize the flow of neural activity in other parts of the brain as well.

Valproic acid affects neurogenesis during early optic tectum development in zebrafish.

The mammalian superior colliculus and its non-mammalian homolog, the optic tectum (OT), are midbrain structures that integrate multimodal sensory inputs and guide non-voluntary movements in response to prevalent stimuli. Recent studies have implicated this structure as a possible site affected in autism spectrum disorder (ASD). Interestingly, fetal exposure to valproic acid (VPA) has also been associated with an increased risk of ASD in humans and animal models. Therefore, we took the approach of determining the effects of VPA treatment on zebrafish OT development as a first step in identifying the mechanisms that allow its formation. We describe normal OT development during the first 5 days of development and show that in VPA-treated embryos, neuronal specification and neuropil formation was delayed. VPA treatment was most detrimental during the first 3 days of development and did not appear to be linked to oxidative stress. In conclusion, our work provides a foundation for research into mechanisms driving OT development, as well as the relationship between the OT, VPA, and ASD. This article has an associated First Person interview with one of the co-first authors of the paper.

A Guide for the Multiplexed: The Development of Visual Feature Maps in the Brain.

Neural maps are found ubiquitously in the brain, where they encode a wide range of behaviourally relevant features into neural space. Developmental studies have shown that animals devote a great deal of resources to establish consistently patterned organization in neural circuits throughout the nervous system, but what purposes maps serve beneath their often intricate appearance and composition is a topic of active debate and exploration. In this article, we review the general mechanisms of map formation, with a focus on the visual system, and then survey notable organizational properties of neural maps: the multiplexing of feature representations through a nested architecture, the interspersing of fine-scale heterogeneity within a globally smooth organization, and the complex integration at the microcircuit level that enables a high dimensionality of information encoding. Finally, we discuss the roles of maps in cortical functions, including input segregation, feature extraction and routing of circuit outputs for higher order processing, as well as the evolutionary basis for the properties we observe in neural maps.